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New Findings Clarify How Kidney Cancer Spreads to Distant Organs

This X-ray image shows metastatic bone tumors in a mouse with kidney cancer. The metastatic tumors appear as hollow or dark areas in the bones.

Summary

Scientists have identified genes and biological mechanisms that one day could be targeted with drugs to stop kidney cancer from spreading to the bone, brain, or other organs.

Metastasis, the process by which some tumors spread from their site of origin to other body parts, accounts for more than nine out of ten cancer-related deaths. But scientists still know relatively little about the genes and biological processes that cause metastasis to occur — information that potentially could translate into new ways to stop cancers from reaching advanced or terminal stages.

Now a Memorial Sloan Kettering research team has shed light on the mechanisms by which kidney cancer metastasizes to distant organs, including the lungs, bone, and brain. Published in the journal Nature Medicine in December, the findings point to potential therapeutic strategies to control the spread of the disease. The study also offers scientific insights that could advance metastasis research in other cancer types.

“In this study, we focused on clear cell renal cell carcinoma, the most common subtype of kidney cancer, for which there is an urgent need for more-effective therapies,” says postdoctoral fellow Sakari Vanharanta, the first author of the Nature Medicine report. “The metastatic form of this disease is almost always incurable.”

In the vast majority of patients, clear cell renal cell carcinoma (ccRCC) tumors carry DNA changes in a gene called VHL. These mutations have been shown to cause the formation of primary kidney tumors, but they do not necessarily lead to metastasis. Until recently, researchers did not know what makes some renal cell carcinoma cells capable of forming secondary tumors in distant organs.

New Potential Drug Targets

In the recent study, the team addressed this question by performing experiments in mouse models and cell lines, and by analyzing biological and clinical data from more than 700 patients with ccRCC, whose tumors had been analyzed in large-scale cancer genomics projects.

They discovered that two genes called CYTIP and CXCR4 are activated in metastatic tumor cells but inactive in non-metastatic cells. Their experiments suggest that the activation of the two genes might be essential for the spread of kidney cancer.

“CXCR4 has been linked to metastasis before in this and other tumor types, including breast cancer,” Dr. Vanharanta says. “Now, our study shows that blocking CXCR4 function with a drug called plerixafor can reduce kidney cancer metastasis in mice.” Plerixafor (MozobilTM) is currently used to stimulate blood stem cells in some cancer patients treated by bone marrow transplantation.

The researchers plan to investigate further whether CXCR4 and CYTIP, and other genes identified in the study, might offer new targets for the development of more-effective drugs for kidney cancer.

Exploring the Epigenetics of Metastasis

In addition, the investigators explored the mechanisms by which the CXCR4 and CYTIP genes are switched on in kidney cancer cells to incite metastasis. Their study revealed that the genes undergo a series of epigenetic changes — modifications in the proteins that package a cell’s DNA and regulate genes.

Epigenetic modifications are commonly seen in many types of cancer and have recently been associated with more-advanced disease. However, little is known about the specific genes and mechanisms by which tumor cells may reconfigure their epigenetic makeup, causing a person’s disease to progress and establish itself in new organs.

“Our study has demonstrated with clear examples how epigenetic alterations can lead to the activation of metastasis-inducing genes,” Dr. Vanharanta notes. “This is a conceptual advancement that is likely to help us understand how metastasis occurs in kidney cancer as well as in other cancer types.”

Comments

Congratulations!!!! to Director Joan Massague and PostDoc Sakari Vanharanta. This text was more understandable for me. Thank You!

Jussi Kantola

Dec 19, 2012 • 1:55 PM

Super research!! Congrats much!

Tiina Malinen-Woodward

Dec 28, 2012 • 2:45 AM

This is what we patients truly need: new approaches, brave research, quick human tests! Thank you for your brilliant work! We live in hope.

Rohinton (Billy) Billimoria

Jan 31, 2013 • 6:02 PM

Congratulations to Director Joan Massague and PostDoc Sakari Vanharanta!! I am a survivor of Renal Cell Carcinoma, which had matastised in my lung, aorta and liver through a clinical trial conducted by Dr. Motzer in 2004-2005 at MSKCC. It has been since then that I have been cured and survived through the clinical trial that gave me Pegalated Interferon. I am also a donor to MSKCC and am glad to see the research projects providing great results. Keep it up, you guys out there can do it and we can soon win the battles against cancer. God Bless!

Sandip Kumar Bajoria

Feb 1, 2013 • 12:42 AM

Congrats to Drs on this valuable research. I am suffering from mRcc with lungs and bones having metastasis. I hope new medicine will come before I die. Sutent and Afinator have failed on me. Any valued advice for my survival will be appreciated. I have also shown to Dr James Heish of Sloan Memorial.

Gautam Sakya

Feb 1, 2013 • 5:11 AM

You have successfully blocked the gene CXCR4 in your laboratory mice to prevent metastasis. I have removed the kidney with ccRCC, stage III pT3a four and half years ago and no clear evidence of metastasis has been found as yet in 6 monthly follow up CT scans. I wish, my RCC is the same type as that of the mice and I would be glad to become a mice for a limited period of time !

David Blount

Feb 19, 2013 • 11:33 AM

I'm struggling with Stage 4 ccRCC that has metastasized to adrenal gland and lower spine (golf ball sized tumor on S1/S2-tail bone). The spinal metastasis has left me totally disabled, without bowel control, inability to urinate, and inability to walk more than about 10 feet. The study results shown here are spectacular. This research won't help repair nerve damage done to my spine, but hopefully I will last long enough on Sutent to receive any benefits from this research. Thank you Drs!

John Smith

Apr 26, 2013 • 6:27 AM

Keep up the good work. I have stage 4 RCC and my hope is that the available treatments can keep me going until this disease can be beaten properly. Your work is appreciated more than you will ever know. Thank you.

William

Nov 18, 2013 • 1:12 PM

My 85 y/o father, in relatively good health, was just Dx with Kidney cancer with metastasis via CT Scan. I do not yet know to where. He is meeting with a Urologist this week and an oncologist next week. Is it 'wise' to perform surgery or chemotherapy in a man of this age? He is the primary caretaker of my 85 y/o mother with dementia, requiring 24/7 'supervision. Please advise. I'll soon know the extent of the metastasis. William

William, unfortunately we are unable to answer specific medical questions on our blog. If you would like to make an appointment with a Memorial Sloan-Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thanks for your comment.

Gerson Goldman

May 16, 2014 • 7:26 AM

What is the status of the experimental program for combating RCC by super charging or complementing the immune system?

We sent your inquiry to Dr. Robert Motzer, one of our medical oncologists who specializes in caring for people with kidney cancer, and he responded, “These new drugs that work by enhancing immune response are in clinical trials and remain experimental. We are currently conducting clinical trials with these agents against kidney cancer in settings selected by clinical trial eligibility.”

Thank you for your comment.

Cindy

Aug 20, 2014 • 11:38 AM

Are there any VEGF inhibitors out there besides Votrient, everolimus, or Inlyta?

Dear Cheri, many survivors get nervous when preparing for follow-up scans (some people call it “scanxiety”.) And cancer recurrence is also a common fear for many people who have been treated for cancer. We have some good information on our website that may be helpful in managing these concerns:

We hope this information is useful and wish you well with your upcoming scans.

Anonymous

Sep 28, 2015 • 12:25 AM

My husband has had bilat kidney cancer one removed and half of the other removed..it has been 5 years now we r pretty sure he has throat cancer his eyesight has been affected as well as the pain from his throat is now affecting his ears. He has a big black spot on the side of his throat and im pretty sure i can feel a mass

Thank you for reaching out. We recommend that your husband discuss these symptoms with his personal physician.

If you would like to make an appointment with a Memorial Sloan Kettering physician for a consultation, please call our Physician Referral Service at800-525-2225 or go to http://www.mskcc.org/cancer­care/appointment. Thanks for your comment.

Constance Lake

Nov 24, 2015 • 4:55 PM

Hello is there any trials in Georgia? My friend has stage iv kidney cancer that has spread to brain , he is 43 and we are in Ocilla , GA. I figured there is more in larger cities just trying to see what's out there

Constance, we’re sorry to hear about your friend’s diagnosis. If he would like to find a clinical trial in Georgia, we recommend he speak to his local oncologist there, or go to www.clinicaltrials.gov, a database maintained by the National Institutes of Health that includes trials around the US and the world. Thank you for your comment.

JamesT. Bergan

May 7, 2016 • 3:34 PM

I recently had a 4 cm malignant tumor removed my right kidney. My doctor told me that and of the encapsulated tumor was removed. Additionally, he removed some of the surrounding tissue during the surgery, which was also found to be absent any cancerous cells.. I still experience tremendous pain after the surgery, so I followed up with multiple procedures and doctors. As a result of the MRI that I took, 3 "spot" were shown to be on my Thoracic spine. one of these was worse than the others, Consequently, I was referred to an oncologist. I don,'t know for sure if the original cancer has metastsised yet - but I would be niave to believe otherwise, I have some questions, if you could answer How could the cancer physically move to the spine without showing a trail or evidence of the travel to the spine, and how could it spread if the encapsulation was not breached during or before my surgery. Is this automatically stage 4 if it is known to be present on the spine, or is this stage designantion dependent on the kidney still being infected Can I hope for greater life expectancy than the estimates I see put forth in the articles I've read?

Cancer cells do not necessarily leave evidence of a trail when they spread from a primary tumor to another site. Metastasis often occurs when cells travel through the bloodstream or through lymph vessels to other areas of the body. (Lymph vessels are much like blood vessels, except they carry a clear fluid called lymph back toward the heart.)

Unfortunately, from the time a tumor begins to form until it is surgically removed, it is shedding tumor cells into the body. Some of these cells have left the primary tumor site and traveled elsewhere in the body before the surgery occurred. Most of these cells die, but a few may not. Metastatic cancer cells can stay dormant — not grow — at a distant site for many years before they begin to grow again. These stragglers can go into hiding, only to flare up later somewhere else — a phenomenon termed latent (or dormant) metastasis. Researchers are just beginning to study how this latent metastasis occurs.

Keep in mind that life expectancy is a general range, not an estimate that applies to an individual person, and the estimates are often based on earlier statistics (before recent treatment advances) and may not reflect current probabilities.

Only a physician can give you more specific information about staging.

If you would like to make an appointment with a Memorial Sloan Kettering physician for a consultation or to discuss possible next steps in your care plan, including clinical trials, please call our Physician Referral Service at:

I am very interested in this new research as my husband has rcc stage 4 mestastised to pancreas. Surgical removal of pancreas would involve 80% and doctor is not sure of even being able to getit all. R radical done 2004 and L partial done in 2015 tunors still in kidney and now this in pancreas. How does he become involved in clinicals and can he been a patient at Sloan Kettering? We live in MA

Dear Janet, we’re very sorry to hear about your husband’s diagnosis. If he is interested in coming to MSK in New York for a consultation and to learn about clinical trial options, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you and your family.

Mandy Paton

Sep 27, 2017 • 6:25 PM

Just had results from first scan after rad neph in June,'small area to be watched',on my lung,also in some fatty tissue behind where kidney was,is this most likely kidney cancer mestasis?leibovich score is 11 ,so I know that's not good

My husband had left kidney removed ... Scan shows he has spots on lungs..... Can you tell me how do you work out when this tumor started and got to 1O cm before it was really noticed.... What would trigger the cells to start multiplying in the first place .... Hope you can help

Dear Trudy, we’re sorry to hear about your husband’s diagnosis. Unfortunately, tumors may grow for many years before they are detected, allowing them to get quite large in some cases and spread to other parts of the body. This is true not just for kidney cancer, but many other types of cancer as well. Scientists are starting to learn some of the reasons that cancer forms, but there are many unanswered questions. This is one of the reasons that research is so important. Thank you for your comment, and best wishes to you and your husband.